Radiolabelled
Baker's Antifolate (BAF) was administered to 6 patients undergoing surgical resection of intracerebral
tumors. Levels of radioactivity in resected
tumor and edematous brain adjacent to
tumor were generally higher than levels in concurrent plasma samples and were generally comparable to levels in temporalis muscle. Levels in
tumor cyst fluid were far lower than concurrent plasma levels and levels in surrounding
tumor. Chromatography was performed on
tumor from 2 patients and revealed that only a small proportion of the radioactivity represented unchanged BAF. The major metabolite present in tissues was 1 000 times less potent as an inhibitor of
dihydrofolate reductase than was BAF. Five patients had cerebrospinal fluid (CSF) sampled following administration of tracer doses of radiolabelled BAF. Radioactivity levels were far lower in CSF than in plasma. Levels of radioactivity in the CSF were also far lower than levels in
tumor and brain samples from other patients and were slightly lower than
tumor cyst fluid levels. Two patients had CSF collected after they received therapeutic doses of BAF. In these patients, both CSF and plasma were assayed using a
dihydrofolate reductase inhibition assay. As with tracer dose studies, CSF concentrations of BAF were substantially lower than were concurrent plasma concentrations. Thus it appears that only very low concentrations of BAF are attainable in human CSF and intracerebral
tumor, although a metabolite which is a very weak inhibitor of
dihydrofolate reductase attains high concentrations in
tumor.